Szmuszkovicz U.S. Pat. No. 4,145,435 discloses some cis- and trans-N-(2-aminocycloaliphatic)-2-arylacetamide derivative compounds, e.g., N-[(N',N'-dimethylamino)cyclohexyl]-N-methyl-2-(4-bromophenyl)acetam ide and trans-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-2-(3,4-dichlorophenyl)acet amide, which have potent analgesic activity; the preferred compounds thereof have, in addition, only low to moderate apparent physical dependence liability compared to morphine and methadone. That Szmuszkovicz '435 patent also describes some prior art patent and publication background that may be of interest herein also.
Also, Szmuszkovicz U.S. Pat. No. 4,098,904 discloses some cis- and trans-N-(2-aminocycloaliphatic)benzamide compounds, e.g., N-methyl-N-(2-aminocycloaliphatic)benzamide compounds, e.g., N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-3,4-dichlorobenzamide which have potent analgesic activity, making them useful for relieving pain in warm blooded animals. That '904 patent also discloses background patents and publications which may be of interest herein.
Lednicer U.S. Pat. No. 4,212,878, discloses some N-[(1-amino-4-(mono- or di-oxygen-group-substituted)cyclohexyl)methyl]benzene-acetamide derivatives, e.g., 2-(3,4-dichlorophenyl)-N[[8-(1-pyrrolidinyl)-1,4-dioxaspiro[4.5]dec-8-yl]m ethyl]acetamide, which also have analgesic drug properties with lower physical dependence liability characteristics than morphine or methadone. That Lednicer patent also refers to what is now Lednicer U.S. Pat. No. 4,065,573 which discloses some 4-amino-4-phenylcyclohexanoneketal compounds, e.g., 4-(m-hydroxyphenyl)-4-(dimethylamino)-cyclohexanone ethylene ketal and 4-(m-hydroxyphenyl)-4-(m-butylmethylamino)cyclohexanone ethylene ketal, which are useful for relieving pain in animals, some of which compounds exhibit narcotic antagonist activity.
A recently filed U.S. application, Ser. No. 06/252,535, filed Apr. 9, 1981, now U.S. Pat. No. 4,360,531, discloses some N-[2-amino-(oxy-group-substituted cycloaliphatic)]phenylacetamide and -benzamide compounds, e.g., trans-3,4-dichloro-N-methyl-[7-(1-pyrrolidinyl)-1,4-dioxaspiro[4.5]-dec-8- yl]benzamide, and salts thereof, as analgesic compounds having low apparent physical dependence liability properties.
Also, recently filed U.S. application Ser. No. 06/252,536, filed Apr. 9, 1981, now U.S. Pat. No. 4,359,476, discloses some N-2-amino-adjacently-oxy-substituted-cycloaliphatic-phenylacetamide and -benzamide compounds, e.g., cis- and trans-4-bromo-N-[3-methoxy-2-(1-pyrrolidinyl)cyclohexyl]-N-methylbenzamide , and cis- and trans-3,4-dichloro-N-methyl-N-[7-(1-pyrrolidinyl)-1,4-dioxaspiro[4.5]-dec- 6-yl]benzamide, and salts thereof, as analgesic compounds having low apparent physical dependence liability properties.
Representative compounds of some of the above types have been or are being studied in advanced animal drug studies. Some concern has been expressed about possible dysphoric side effects of such compounds when used as analgesic drugs. Those skilled in the art continue to search for new and more potent and otherwise advantageous analgesic compounds.